Tekturna HCT

INDICATIONS

Tekturna HCT is indicated for
the treatment of hypertension, to lower blood pressure. Lowering blood pressure
reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes
and myocardial infarctions. These benefits have been seen in controlled trials
of antihypertensive drugs from a wide variety of pharmacologic classes
including hydrochlorothiazide. There are no controlled trials demonstrating
risk reduction with Tekturna HCT.

Control of high blood pressure
should be part of comprehensive cardiovascular risk management, including, as
appropriate, lipid control, diabetes management, antithrombotic therapy,
smoking cessation, exercise, and limited sodium intake. Many patients will
require more than one drug to achieve blood pressure goals. For specific advice
on goals and management, see published guidelines, such as those of the
National High Blood Pressure Education Program's Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive
drugs, from a variety of pharmacologic classes and with different mechanisms of
action, have been shown in randomized controlled trials to reduce
cardiovascular morbidity and mortality, and it can be concluded that it is
blood pressure reduction, and not some other pharmacologic property of the drugs,
that is largely responsible for those benefits. The largest and most consistent
cardiovascular outcome benefit has been a reduction in the risk of stroke, but
reductions in myocardial infarction and cardiovascular mortality also have been
seen regularly.

Elevated systolic or diastolic
pressure causes increased cardiovascular risk, and the absolute risk increase
per mmHg is greater at higher blood pressures, so that even modest reductions
of severe hypertension can provide substantial benefit. Relative risk reduction
from blood pressure reduction is similar across populations with varying
absolute risk, so the absolute benefit is greater in patients who are at higher
risk independent of their hypertension (for example, patients with diabetes or
hyperlipidemia), and such patients would be expected to benefit from more
aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs
have smaller blood pressure effects (as monotherapy) in black patients, and
many antihypertensive drugs have additional approved indications and effects
(e.g., on angina, heart failure, or diabetic kidney disease). These
considerations may guide selection of therapy.

Add-On Therapy

A patient whose blood pressure
is not adequately controlled with aliskiren alone or hydrochlorothiazide alone
may be switched to combination therapy with Tekturna HCT.

A patient whose blood pressure
is controlled with hydrochlorothiazide alone but who experiences hypokalemia
may be switched to combination therapy with Tekturna HCT.

A patient who experiences
dose-limiting adverse reactions on either component alone may be switched to
Tekturna HCT containing a lower dose of that component in combination with the
other to achieve similar blood pressure reductions.

Replacement Therapy

Tekturna HCT may be substituted
for the titrated components.

Initial Therapy

Tekturna HCT may be used as initial therapy in patients
who are likely to need multiple drugs to achieve their blood pressure goals.

The choice of Tekturna HCT as initial therapy should be
based on an assessment of potential benefits and risks. Patients with Stage 2
hypertension are at a relatively high risk for cardiovascular events (such as
strokes, heart attacks, and heart failure), kidney failure, and vision
problems, so prompt treatment is clinically relevant. The decision to use a
combination as initial therapy should be individualized and should be shaped by
considerations such as baseline blood pressure, the target goal, and the incremental
likelihood of achieving goal with a combination compared to monotherapy.
Individual blood pressure goals may vary based upon the patient's risk.

Data from the high-dose multifactorial study [see Clinical
Studies] provide estimates of the probability of reaching a target blood
pressure with Tekturna HCT compared to aliskiren or hydrochlorothiazide
monotherapy. The figures below provide estimates of the likelihood of achieving
systolic or diastolic blood pressure control with Tekturna HCT 300/25 mg, based
upon baseline systolic or diastolic blood pressure. The curve of each treatment
group was estimated by logistic regression modeling. The estimated likelihood
at the right tail of each curve is less reliable because of small numbers of
subjects with high baseline blood pressures.

At all levels of baseline blood
pressure, the probability of achieving any given diastolic or systolic goal is
greater with the combination than for either monotherapy. For example, the mean
baseline msSBP/msDBP for patients participating in this multifactorial study
was 154/99 mmHg. A patient with a baseline blood pressure of 154/99 mmHg has
about a 62% chance of achieving a goal of < 140 mmHg (systolic) and 61%
chance of achieving < 90 mmHg (diastolic) on aliskiren alone, and the chance
of achieving these goals on hydrochlorothiazide alone is about 54% (systolic)
and 49% (diastolic). The chance of achieving these goals on Tekturna HCT rises
to about 77% (systolic) and 74% (diastolic). The chance of achieving these
goals on placebo is about 34% (systolic) and 37% (diastolic) [see DOSAGE AND
ADMINISTRATION and Clinical Studies].

DOSAGE AND ADMINISTRATION

Dose Selection

The recommended once-daily doses of Tekturna HCT in order
of increasing mean effect are 150/12.5 mg, 150/25 mg or 300/12.5 mg, and 300/25
mg.

Dose Titration

The antihypertensive effect of Tekturna HCT is largely
manifested within 1 week, with maximal effects generally seen at around 4
weeks. If blood pressure remains uncontrolled after 2 to 4 weeks of therapy,
the dose may be titrated up to a maximum of aliskiren 300
mg/hydrochlorothiazide 25 mg.

Add-On Therapy

A patient whose blood pressure is not adequately
controlled with aliskiren alone or hydrochlorothiazide alone may be switched to
combination therapy with Tekturna HCT. The usual recommended starting dose is
150/12.5 mg once daily as needed to control blood pressure. The dose may be
titrated up to a maximum of aliskiren 300 mg/hydrochlorothiazide 25 mg once
daily.

Replacement Therapy

Tekturna HCT may be substituted for the individually
titrated components.

Initial Therapy

The usual recommended starting dose is 150/12.5 mg once
daily as needed to control blood pressure. The dose may be titrated up to a
maximum of aliskiren 300 mg/hydrochlorothiazide 25 mg once daily. Tekturna HCT
is not recommended for use as initial therapy in patients with intravascular
volume depletion [see WARNINGS AND PRECAUTIONS].

Use with Other Antihypertensive Drugs

Tekturna HCT may be administered with some other
antihypertensive agents. In diabetics, do not use in combination with
angiotensin receptor blockers (ARBs) or angiotensin converting enzyme
inhibitors (ACEIs) [see CONTRAINDICATIONS]. Concomitant use of aliskiren
with an ARB or ACEI is not recommended in patients with GFR < 60 ml/min [see WARNINGS
AND PRECAUTIONS]. There are no data available with use of Tekturna HCT with
angiotensin-converting enzyme inhibitors or beta blockers [see Clinical
Studies].